Related Experiment Video

Updated: Feb 2, 2026

Using an Automated Cell Counter to Simplify Gene Expression Studies: siRNA Knockdown of IL-4 Dependent Gene Expression in Namalwa Cells
10:34

Using an Automated Cell Counter to Simplify Gene Expression Studies: siRNA Knockdown of IL-4 Dependent Gene Expression in Namalwa Cells

Published on: April 14, 2010

16.0K

TET2 coactivates gene expression through demethylation of enhancers

Lu Wang1,2, Patrick A Ozark1,2, Edwin R Smith1,2

  • 1Simpson Querrey Center for Epigenetics, Northwestern University Feinberg School of Medicine, 320 East Superior Street, Chicago, IL 60611, USA.

Science Advances
|November 13, 2018
PubMed

Insights

The tet methylcytosine dioxygenase 2 (TET2) enzyme plays a key role in gene regulation by demethylating DNA. Loss of TET2 impacts DNA methylation and the estrogen response, revealing a crucial epigenetic axis.

Area of Science:

  • Epigenetics
  • Molecular Biology
  • Cancer Biology

Background:

  • The TET2 enzyme modifies DNA by converting 5-methylcytosine to 5-hydroxymethylcytosine.
  • TET2 mutations are common in human cancers, altering DNA methylation and gene expression.
  • Understanding TET2's role in gene regulation is crucial for cancer research.

Purpose of the Study:

  • To investigate the role of TET2 in regulating gene expression at active enhancers.
  • To elucidate the mechanism by which TET2 influences the estrogen response.
  • To identify interactions between TET2, estrogen receptor α (ERα), and other epigenetic modifiers.

Main Methods:

  • Development and application of TET2-specific antibodies.
  • Utilizing the estrogen response as a model system.
  • CRISPR-Cas9 gene editing to knockout TET2.
  • Analysis of DNA methylation patterns at enhancers.
  • Investigating protein-protein interactions involving TET2 and ERα.

Main Results:

  • Endogenous TET2 localizes to active enhancers and recruits ERα.
  • TET2 knockout globally increases enhancer DNA methylation, impairing the estrogen response.
  • A positive feedback loop between TET2 and ERα, dependent on MLL3 COMPASS, was identified at enhancers.
  • DNA demethylation by TET2 is essential for enhancer activation and transcriptional regulation.

Conclusions:

  • TET2 acts as a key epigenetic regulator at active enhancers.
  • TET2 facilitates the estrogen response by recruiting ERα and maintaining enhancer demethylation.
  • An epigenetic axis involving TET2, ERα, and MLL3 COMPASS coordinates gene expression programs.

More Related Videos

Author Spotlight: Advancing Gene Editing in Bamboo Leaves for Sustainable Plastic Alternatives06:57

Author Spotlight: Advancing Gene Editing in Bamboo Leaves for Sustainable Plastic Alternatives

Published on: August 18, 2023

2.3K
A Web-Based Workflow for Selecting Gene- and Tissue-Specific Enhancers08:12

A Web-Based Workflow for Selecting Gene- and Tissue-Specific Enhancers

Published on: July 18, 2025

663

Related Concept Videos

What is Gene Expression?01:42

What is Gene Expression?

Overview
Gene expression is the process in which DNA directs the synthesis of functional products, that is, proteins. Cells can regulate gene expression at various stages. It allows organisms to generate different cell types and enables cells to adapt to internal and external factors.
Genetic Information Flows from DNA to RNA to Protein
A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is made up of nucleotides and proteins consist of amino...
196.7K
What is Gene Expression?01:36

What is Gene Expression?

A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is comprised  of nucleotides and proteins are comprised of amino acids, a mediator is required to convert the information encoded in DNA into proteins. This mediator is the messenger RNA (mRNA). mRNA copies the blueprint from DNA by a process called transcription. In eukaryotes, transcription occurs in the nucleus by complementary base-pairing with the DNA template. The mRNA is then...
11.4K
Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
16.5K
Cell Specific Gene Expression01:58

Cell Specific Gene Expression

5.6K
Chromatin Position Affects Gene Expression02:35

Chromatin Position Affects Gene Expression

Chromatin is the massive complex of DNA and proteins packaged inside the nucleus. The complexity of chromatin folding and how it is packaged inside the nucleus greatly influences  access to genetic information. Generally, the nucleus' periphery is considered transcriptionally repressive, while the cell's interior is considered a transcriptionally active area. 
Topologically Associated Domains (TADs)
The 3-dimensional positioning of chromatin in the nucleus influences the...
24.8K
mRNA Stability and Gene Expression02:51

mRNA Stability and Gene Expression

The structure and stability of mRNA molecules regulates gene expression, as mRNAs are a key step in the pathway from gene to protein. In eukaryotes, the half-life of mRNA varies from a few minutes up to several days. mRNA stability is essential in growth and development. The absence of the proteins regulating its stability, such as tristetraprolin in mice, can cause systemic issues, including bone marrow overgrowth, inflammation, and autoimmunity.
Cis-acting Elements involved in mRNA stability
6.7K